1. Field of the Invention
The present invention relates to optical analyte sensors; more specifically, to sensors configured to accommodate submicroliter liquid sample volumes in the rapid detection of analytes in such samples.
2. Description of the Prior Art
Portable analyte monitoring devices, such as portable blood glucose monitors, typically require sensors for the quantification of analytes in biological samples. These sensors are designed to receive fluid samples from their users and are oftentimes discarded after each use. The frequent purchase and use of such sensors has become an indispensible part of the lives of many diabetics. Individuals with Type 1 diabetes are often advised to measure their blood glucose levels three or more times per day. However, the pain associated with blood sample collection and the frequency of such measurements, which necessitate the purchase of numerous sensors, cause many diabetics to falter from their suggested monitoring schedules. The prior art has sought to remedy these complications by operating on less blood from their users and favoring design features that lower the cost of such sensors. Features that lead to more rapid test results can also result in more frequent self-monitoring.
U.S. Pat. Nos. 4,935,346, 5,049,487, 5,059,394, 5,179,005 and 5,304,468 to Phillips et al. discloses various methods and devices for applying a sample of whole blood to the “sample” side of a sensor membrane that is impregnated with the necessary reagents. Red blood cells are then separated by this membrane as the remaining sample migrates toward the “testing” side of the membrane. The glucose in the remaining sample then interacts with the reagents to produce a light-absorbing reaction product. An optical measurement instrument can then be used to measure the color change which correlates to the blood glucose level in the sample. U.S. Pat. No. 5,972,294 to Smith et al. discloses a reagent sensor dependent on a membrane for receiving a fluid sample and separating red blood cells from such a sample before an assay is performed. U.S. Pat. Nos. 5,296,192 and 6,040,195 to Carroll et al. describe an improved multi-layered sensor for receiving a whole blood sample. The sensor includes filtration layers to remove red blood cells, fluid volume control dams to prevent spillage of the fluid from the sensor, and a chemical reagent formulation that facilitates end-point testing. U.S. Pat. No. 6,924,093 to Haviland et al. discloses an alignment notch added to a sensor and an obround-shaped aperture for receiving fluid samples. Both features are intended to reduce the amount of a fluid sample needed to provide an assay. Haviland indicates that the purpose of the alignment notch is to facilitate proper alignment of the sensor within a measuring instrument such that the sample-receiving aperture is accurately aligned over the instrument's light source. Prior to such an improvement, sensors compensated for the likelihood of misalignment by providing a larger measurement area in the form of a larger aperture. Such an aperture naturally required a greater sample volume to saturate.
While the aforementioned sensors are all widely used, they share some common limitations. First, since blood from a diabetic patient must be applied to either a top “sample” layer or a top-facing aperture of the aforementioned sensors, 3 μL to 50 μL of blood must be obtained from a patient using such a sensor. A patient must often obtain any sample volume larger than 3 μL by lancing the skin on his or her fingertips and, subsequently, milking the area to obtain a useful sample volume. This procedure is a nuisance for the patient and is often painful. Less painful methods for obtaining a sample include lancing the arm or thigh, both of which have a lower nerve ending density than fingertips. However, lancing the body in such regions often produces inadequate sample volumes because these regions are not heavily inundated with the necessary blood vessels. In addition, most current sensors are not designed to accept blood from these regions of the body due to the restricted accessibility of these regions of the body to the sample area on the sensor. Although U.S. Pat. No. 6,099,484 to Douglas et al. has aimed to solve this problem by using a capillary device as a wick to transfer fluid samples to the sensor pad, adding the capillary device disclosed by Douglas to most sensors would be impractical and increase the cost of such sensors prohibitively.
Moreover, since the analyte of interest is often measured by a light signal reflected off the surface of a sensor where a color reaction has taken place, the sensor has to be inserted into an optical measurement instrument's protective shroud during testing to avoid interference from environmental or ambient light. This also requires that the surface of the sensor be closely placed near the light source and the light detector of the instrument. Repeated testing could potentially result in contamination of the instrument by blood or other biological fluids and lead to inaccurate test results.
Finally, another desired feature for a self-monitoring system is to obtain the results of such measurements rapidly, for example, in less than three seconds. Diabetic patients normally measure their glucose levels before each meal. Obtaining the results of such measurements rapidly is always desired, especially for patients who are children.
To overcome these limitations, it is desirable to develop a sensor that requires minimal sample volume, reduces contamination to measurement instruments, exhibits a measurable change in optical properties rapidly, and is capable of using not only blood samples from fingertips but also blood samples from other parts of the body, such as the arm and thigh, which have lower nerve ending densities making the sampling process less painful or even painless. Over the past two decades, a wide variety of optical sensors have been proposed for analysis of chemical species in industrial, environmental and biological samples. These sensors operate by detecting optical changes of a sensing material or indicator dye on interaction with an analyte. Due to the variety of analyte-specific indicators available, such sensors may be used for monitoring a large number of analytes, including blood glucose levels for patients with diabetes.
For example, U.S. Pat. No. 5,859,937 to Nomura disclosed a sensor comprising an atomic oxygen etched optical fiber with analyte-responsive reagents deposited on the etched surface. The analyte concentration was measured by physical or chemical response upon being contacted with the reagents. However, optical fiber surface etching described in the patent is not practical for making reproducible and reliable sensors. Raskas in U.S. Pat. No. 6,157,442 described a micro optical fiber sensor device, but it is only for in vivo use.
The current invention discloses a novel reflectance optical sensor that utilizes submicroliter sample volumes for analyte detection and quantitative determination within three seconds of time. The new invention also discloses a sample collecting storage chamber and capillary passage which improve the accuracy and reliability of such measurements when used with standard optical measurement instruments.